Decarboxylative chlorination

Bu3PO is also a catalyst for decarboxylative chlorination of alcohols by phosgene (equa-tion 171)1093. 

The first enantiospecific route to this class of natural products was reported by Williard and de Laszlo (Scheme 43.47). The route started with the a,a-dichlorination of aldehyde 298 with enamine formation followed by chlorination with A-chlorosuccinimide (NCS) to afford 299 in 72% yield. The subsequent oxidation of aldehyde 299 with KMn04, followed by Kochi-Hunsdiecker decarboxylative chlorination of resultant carboxylic acid 300, afforded trichloromethyl ester 301 in 77% yield. Ester 301 was divergently converted into aldehyde 302 and carboxylic acid 303, both of which were mixed with thiazol-2-ylmethyl isocyanide and MeNH2 to promote Ugi condensation to yield (+)-demethyldysidenin 304, an enantiomer of the natural product, along with the C5-epiner. This work has led to the... 

It was first described in 1608 when it was sublimed out of gum benzoin. It also occurs in many other natural resins. Benzoic acid is manufactured by the air oxidation of toluene in the liquid phase at 150°C and 4-6 atm. in the presence of a cobalt catalyst by the partial decarboxylation of phthalic anhydride in either the liquid or vapour phase in the presence of water by the hydrolysis of benzotrichloride (from the chlorination of toluene) in the presence of zinc chloride at 100°C. 

Nitromethane, CH3NO2, the first member of the homologous series, can, however, be readily prepared by a special reaction. When equimolecular amounts of sodium nitrite and sodium monochloroacetate are heated together in aqueous solution, the chlorine in the monochloroacetate is replaced by the nitro group, and the sodium nitroacetate thus formed undergoes hydrolysis follow ed by decarboxylation ... 

In 1869 Berthelot- reported the production of styrene by dehydrogenation of ethylbenzene. This method is the basis of present day commercial methods. Over the year many other methods were developed, such as the decarboxylation of acids, dehydration of alcohols, pyrolysis of acetylene, pyrolysis of hydrocarbons and the chlorination and dehydrogenation of ethylbenzene." ... 

Acyl radicals can fragment with toss of carbon monoxide. Decarbonylation is slower than decarboxylation, but the rate also depends on the stability of the radical that is formed. For example, when reaction of isobutyraldehyde with carbon tetrachloride is initiated by t-butyl peroxide, both isopropyl chloride and isobutyroyl chloride are formed. Decarbonylation is competitive with the chlorine-atom abstraction. 

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

Another decarboxylation reaction that employs lead tetraacetate under milder conditions, has been introduced by Grob et alJ In that case A-chlorosuccinimide is used as chlorinating agent and a mixture of A,A-dimethylformamide and acetic acid as solvent. 

Nucleophilic displacement of chlorine in A -chloroalkyloxadiazolinethiones, decarboxylation of iV-alkoxycarbonylox-adiazolinones, reduction of (nitroaryl)oxadiazolinones to (aminoaryl)oxadiazolinones, and reactions of carbonyldi-imides, derived from oxadiazolinethiones, with nucleophiles have been described earlier <1996CHEC-II(4)268>. 

While some phenol is produced by the nucleophilic substitution of chlorine in chlorobenzene by the hydroxyl group (structure 17.17), most is produced by the acidic decomposition of cumene hydroperoxide (structure 17.18) that also gives acetone along with the phenol. Some of the new processes for synthesizing phenol are the dehydrogenation of cyclohexanol, the decarboxylation of benzoic acid, and the hydrogen peroxide hydroxylation of benzene. 

A tetrahydropyrido[3,4-/)]pyrazine nucleus was constructed from 2,3-dimethylpyrazine 687 by chlorination with A-chlorosuccinimide (NCS) to give 2,3-bis(chloromethyl)pyrazine 688, followed by cyclization with diethyl acet-amidomalonate to pyridopyrazine 689. Hydrolysis and decarboxylation of 689 in hydrochloric acid, then esterification by action of thionyl chloride in methanol gave methyl 5,6,7,8-tetrahydropyrido[3,4-. ]pyrazine-7-carboxylate hydrochloride 690 (Scheme 32) <2003BMC433>. 

Reports of electrophilic substitution are scarce, but pyridazino[2,3-. ]quinoxaline-4,4-dicarboxylates reportedly undergo bromination and chlorination at C-3 with A -halosuccinimides in acetic acid (Scheme 29). Treatment of the product with hydrazine hydrate results in hydrolysis and mono-decarboxylation <2003JHC837>. 

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